Volodymyr Ohryzko -- a career diplomat and candidate for foreign minister -- had pledged to move Ukraine closer to the West.
Ohryzko received 196 of the 226 votes needed for confirmation.
The Verkhovna Rada also rejected the nomination of Viktor Korol to head Ukraine's security services. Korol is a lawmaker from Yushchenko's Our Ukraine bloc who has served as deputy interior minister and head of the tax police.
Korol received 190 votes.
Roman Zvarych, Yushchenko's representative to the parliament, said the president will consider resubmitting the two nominations.
"The Ukrainian president is not constrained by anything in proposing this candidacy [once gain] even though the Verkhovna Rada made such a decision after his first proposal," Zvarych said. "Under the constitution, the president can propose the same candidates for these positions again."
The nomination battles are part of an ongoing confrontation between President Yushchenko's pro-Western supporters and backers of pro-Moscow Prime Minister Viktor Yanukovich.
The pro-presidential party Our Ukraine and the Yuliya Tymoshenka Bloc supported both Ohryzko and Korol.
Yanukovych's Party of Regions, the Socialist Party, and the Communist Party opposed both choices.
(with material from agency reports)